Association of TP53 germline variant and choledochal cyst among clinically diagnosed Filipino pediatric patients

@#Background and Objective. Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital. Methods. Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing. Results. A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40). Conclusion. There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.

Tratamiento quirúrgico inmediato en niños con perforación espontánea de la vía biliar. Experiencias de 16 años

Introducción: La perforación espontánea de los conductos biliares es una rara enfermedad caracterizada por una disrupción no traumática de la vía biliar en pacientes aparentemente sanos. Se trata de una grave situación potencialmente letal, pero diagnosticada y tratada correctamente tiene un pronóstico excelente. Objetivo: Caracterizar los principales elementos clínico-quirúrgicos expresados en una serie de 5 pacientes operados en un servicio de referencia nacional. Presentación de casos: Se presenta la experiencia con una serie de casos en 16 años en una sola institución. La afección se observó en niñas recién nacidas y lactantes con una edad media de 4 meses, y se presentó desde la clínica como una colestasis acompañada de distensión abdominal, ascitis biliar, acolia, y signos de irritación peritoneal. El 80 % de los casos se intervinieron en el hospital "William Soler", y en un caso se ejecutó el procedimiento después de una laparotomía por una posible apendicitis aguda, en otro hospital. El diagnóstico se basó en el cuadro clínico descrito, la ecografía abdominal, la paracentesis con medición del índice bilirrubina líquido ascítico/bilirrubina sérica, y la colangiografía intraoperatoria. La cirugía definitiva se realizó inmediatamente, y consistió en: lavado peritoneal, colangiografía diagnóstica, reparación hepaticoyeyunostomía en Y de Roux y colocación de drenaje. Conclusiones: El tratamiento realizado resulta eficaz y seguro en todos los casos, con una excelente evolución, sin complicaciones importantes y con una total supervivencia posoperatoria. La colangiografía intraoperatoria permitió identificar el sitio de la perforación y diagnosticar malformaciones asociadas como dilataciones biliares congénitas y anomalías de la unión bilio-pancreática.

Introduction: Spontaneous bile duct perforation is a rare condition characterized by non-traumatic disruption of the bile duct in apparently healthy patients. It is a serious potentially lethal situation, but correctly diagnosed and treated its prognosis is excellent. Objetive: To characterize the main clinical-surgical elements expressed in a series of 5 patients operated in a national referral service. Case presentation: The experience with a series of cases during a period of 16 years in a single institution is presented. The condition was observed mainly in newborn girls and infants with an average age of 4 months, and presented clinically as cholestasis accompanied by abdominal distension, biliary ascites, acholia, and signs of peritoneal irritation. 80% of the cases were operated primarily in the "William Soler" hospital, and in one case the procedure was performed after a laparotomy for a possible acute appendicitis, in another hospital. The diagnosis was based on the clinical picture described, abdominal ultrasound, paracentesis with measurement of the ascitic liquid bilirubin/serum bilirubin index, and intraoperative cholangiography. Definitive surgery was performed immediately and consisted of: peritoneal lavage, diagnostic cholangiography, Roux-en-Y liver and jejunostomy repair and drainage placement. Conclusions: The treatment performed was effective and safe in all cases, with an excellent evolution, no major complications and total postoperative survival. Intraoperative cholangiography made it possible to identify the site of perforation and to diagnose associated malformations such as congenital biliary dilatations and anomalies of the biliary-pancreatic junction.

A case of X-linked hyper IgM syndrome with a novel CD 40LG mutation / 中华实用儿科临床杂志

A retrospective analysis was performed on the clinical data of a child with X-linked hyper IgM syndrome (XHIGM) with cholangiectasis as a major manifestation in Children′s Hospital of Fudan University in March 2017.The patient was a 4-year-old boy who was admitted to the hospital due to repeated diarrhea for half a year and yellow skin for 5 days.No abnormalities were found in his fetal period and birth history; The patient had 2 severe pneumonias and suppurative infection of the left axillary lymph node in infancy.Physical examination revealed delayed physical development, severe malnutrition, moderately stained yellow, lymphadenopathy and hepatomegaly.Laboratory examinations showed elevated leukocyte, eosinophils and C-reactive protein, low hemoglobin and albumin, high gamma-glutamyl transpeptidase (GGT), low IgG and normal IgM.Imaging examination revealed diffuse expansion of intrahepatic and extrahepatic bile ducts.Hepatic pathology showed hyperplasia in the bile canaliculus and some fibrous tissues around the large bile ducts.High-throughput sequencing identified a pathogenic mutation in the XHIGM gene CD 40LG (exon5 c. 506A>G, p.Y169C), with his mother as a carrier.After admission, the patient was given anti-infection, diet adjustment, albumin, intravenous immunoglobulin and ursodeoxycholic acid.The patient was discharged after the improvement in his condition.This case suggested that in addition to the common infection characteristics, XHIGM can also be manifested as diffuse intrahepatic, extrahepatic cholangiectasis and significantly elevated eosinophil.c.506A>G mutation in CD 40LG was the pathogenic mutation of this disease.

Clinical value of endoscopic ultrasonography in diagnosis and treatment of common bile duct dilatation / 中华消化内镜杂志

Objective To investigate the value of endoscopic ultrasonography(EUS)in the diagnosis and treatment of undetermined etiology of common bile duct (CBD) dilatation. Methods Patients, who were referred for dilated CBD but unable to identify the cause by imaging, underwent EUS for the diagnosis of etiology in Endoscopy Center of Zhongshan Hospital Affiliated to Fudan University from December 2015 to December 2016. The therapy was on the basis of diagnosis of EUS. Final diagnoses were determined by surgical pathology or follow-up for at least 3 months. Results A total of 76 patients were included in the study. The sensitivity, specificity and accuracy of EUS for patients with choledocholithiasis,patients with ampullary tumor, and patients with inflammatory stenosis were 100.0%(7/7), 100.0%(69/69), 100.0%(76/76), and 88.0%(22/25), 92.2%(47/51), 90.8%(69/76),and 90.9%(40/44), 93.8%(29/32), 90.8%(69/76), respectively. Accuracy of EUS for etiological diagnosis of CBD dilatation was 90.8%(69/76). The sensitivity,specificity and accuracy of EUS combined with tumor markers for patients with malignant CBD dilatation were 96.0%(24/25), 96.1%(49/51),and 96.1%(73/76), respectively. Conclusion EUS is an effective method for the etiological diagnosis of CBD dilatation and has guiding significance for the treatment. EUS combined with tumor markers may benefit differential diagnosis of benign and malignant CBD dilatation.

Analysis on the incidence of bile duct dilatation after open and laparoscopic cholecystectomy / 中国现代普通外科进展

Objective:To investigate the open method(OC) and laparoscopic cholecystectomy (LC) after bile duct dilation incidence of contrast.Methods:collected from 2006 December to 2014 December in the department of hepatobiliary surgery requires 412 patients underwent cholecystectomypatients hospitalized with cholecystolithiasis,chronic cholecystitis,gallbladderpolyps,were randomly divided into LC group and OC group,LC group of 207 cases,205 cases in OC group,and were respectively treated with LC and OC.Start regular follow-up after a month,the comparison of 2 surgical operation time,blood loss and postoperative application of antibiotics time,anus exhaust time,eating time and hospitalization time.And to observe the two groups the incidence of patients after bile duct dilatation in follow-up after operation.Results:207 cases of LC patients were 89 patients had bile duct dilation,205 cases of OC patients were 41 patients had bile ductdilation,statistically significant differences between the two groups (P＜0.05).In group LC,the diameter of common bile duct in operation half months began to increase,the increase continued until 3 months after operation.After 3 months of little change in the diameter of common bile duct.The averagepreoperative bile duct diameter is 5.3 mm,after 6.1 mm,there was significant difference(P＜0.01).Conclusion:LC is a safe and reliable operation method,Identifying cause dilatation of common bile duct after LC operation and attention as soon as possible to give the corresponding prevention and treatment,further can reduce complications occur.

Diagnosis and treatment of type Ⅰ congenital biliary dilatation / 中华肝胆外科杂志

Type Ⅰ congenital biliary dilatation is a congenital biliary duct defect disease.It is also called congenital choledochocele cyst (CCC).Endoscopic ultrasonography (EUS),magnetic resonance cholangiopacreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are very important for the diagnosis.Operation is generally regaded as the best choose.It is recommended that cholecystectomy + choledochal cyst excision + hepatic duct jejunum Roux-Y anastomosis is the chief therapeutic method.This article reviews the pathogenesis,classifications,diagnosis and treatment of the disease.

Postoperative Change of Intrahepatic Bile Duct Dilatation in Choledochal Cyst

Choledochal cyst is a congenital dilatation of the bile duct. Intrahepatic bile duct dilatation of type IVa by Todani's classification at the time of diagnosis resolved spontaneously after cyst excision and hepaticojejunostomy in many cases. It should be distinguished from the true cystic dilatation of the intrahepatic ducts, which tends to persist, albeit after some regression. We therefore studied postoperative intrahepatic duct dilatation changes in choledochal cyst. A total of seventy-six choledochal cysts were managed at the Division of Pediatric Surgery, Department of Surgery, Samsung Medical Center from May 1995 to December 2005. The ratio of males to females was 1:2.8. Preoperative radiologic diagnosis by Todani's classification was Type I (n=52, 68.4 %), II (n=1, 1.3 %), IVa (n=23, 30.3 %). Among fifty-five patients with intrahepatic bile duct dilatation we were able to follow up forty-eight by ultrasonography. Twenty-two patients were type IVa, and twenty-six patients were type I and showed intrahepatic duct dilatation. Mean follow-up duration was 35.3 months (9~105 months). Complete regression of dilated intrahepatic duct was observed in fifteen patients of type IVa and twenty-four patients of type I. Incomplete regression of dilated intrahepatic duct was observed in six patients in type IVa and two patients in type I. Only one patient in type IVa showed no change in ductal dilatation during a follow-up period of 15 months. We conclude that true type IVa is much less frequent than what was diagnosed preoperatively by imaging study. Therefore in type IVa patients who are diagnosed preoperatively the decision to perform liver resection should be carefully considered. Postoperative long term follow up of choledochal cyst with intrahepatic bile duct dilation is needed.

Management Strategy for Congenital Choledochal Cyst with Co-existing Intrahepatic Dilation and Aberrant Bile Duct As Well As Other Complicated Biliary Anomalies

The purpose of this study was to investigate and discuss imaging methods and management strategies for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies. In this study we reviewed and analyzed 72 patients with congenital choledochal cyst, ranging in age from 15 days to 12 years old and who were seen at our hospital during the past 12 years, from January 1993 to October 2005. The image manifestation and clinical significance of patients with co- xisting intrahepatic biliary dilation and aberrant bile duct were carefully examined during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of the cystic type. That is, the orifice of the dilated intrahepatic tract that converged into the common hepatic duct showed membrane or septum-like stenosis. In 10 cases the dilation tapered off from the porta hepatis to the initiating terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left hepatic ducts converged at the choledochal cyst. In conclusion, the imaging methods for intrahepatic bile duct dilation possess important clinical significance. Further, for hepatojejunostomy with radical excision of a choledochal cyst, additional operative procedures for intrahepatic stenosis, possible bile duct malformation and pancreaticobiliary common duct calculi can potentially reduce postoperative complications.

Management Strategy for Congenital Choledochal Cyst with Co-existing Intrahepatic Dilation and Aberrant Bile Duct As Well As Other Complicated Biliary Anomalies

The purpose of this study was to investigate and discuss imaging methods and management strategies for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies. In this study we reviewed and analyzed 72 patients with congenital choledochal cyst, ranging in age from 15 days to 12 years old and who were seen at our hospital during the past 12 years, from January 1993 to October 2005. The image manifestation and clinical significance of patients with co- xisting intrahepatic biliary dilation and aberrant bile duct were carefully examined during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of the cystic type. That is, the orifice of the dilated intrahepatic tract that converged into the common hepatic duct showed membrane or septum-like stenosis. In 10 cases the dilation tapered off from the porta hepatis to the initiating terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left hepatic ducts converged at the choledochal cyst. In conclusion, the imaging methods for intrahepatic bile duct dilation possess important clinical significance. Further, for hepatojejunostomy with radical excision of a choledochal cyst, additional operative procedures for intrahepatic stenosis, possible bile duct malformation and pancreaticobiliary common duct calculi can potentially reduce postoperative complications.

Diagnostic Use of Endoscopic Ultrasonography in the Evaluation of Common Bile Duct Dilatation / 대한소화기내시경학회지

BACKGROUND/AIMS: The aim of this study was to assess the diagnostic use of endoscopic ultrasonograpy (EUS) in detecting the cause of common bile duct (CBD) dilatation in patients in whom abdominal ultrasonography or abdominal CT scan could not identify the cause of dilatation. METHODS: Thirty-seven patients (23 men, 14 women, mean age 62.2 years) with uncertain causes of CBD dilatation on abdominal sonogram and CT scan between October 1999 and November 2003 were enrolled. All patients were evaluated by EUS and endoscopic retrograde cholangiopancreatography (ERCP). Final diagnosis were determined by ERCP, surgical exploration and clinical follow-up. RESULTS: The following diagnosis were made by EUS: choledocholithiasis in 11 patients, CBD dilatation only in 12, benign stricture of distal CBD in 8, periampullary tumor in 6. The definitive diagnosis of choledocholithiasis (n=11), benign stricture of distal CBD (n=10), ampullary tumor (n= 5) were determined by ERCP with or without sphincterotomy and surgical exploration. EUS provided the accurate explanation for CBD dilatation in 32 of the 37 patients (86%). CONCLUSIONS: When the diagnosis of biliary obstruction remains obscure on abdominal sonography or CT scan, EUS may be useful.

Jejunal interposition hepatico-duodenostomy in the treatment of congenital dilatation of bile duct

his technique was performed on 50 patients with congenital dilatation of the bile duct including 35 females and 15 males, ranging in age from 3 months to 33 years old. Patients treated from 4/1996 to 6/1999 at the Pediatric Institute and at the Bach mai Hospital, with abdominal pain in 76%, jaundice in 58%, classic triad in 12%. The diagnosis and the indications for operation have based on the ultrasonography.The cyst flattened by bile suction and the intraoperative cholangiography was very useful for the dissection, the resection of cysts and the performance of the anastomosis. There were not particular difficulties to prepare a jejunal segment about 25 cm in length, 40-50 cm from Treitz, passing through a hole made in the transverse mesocolon and duodenum. 35 intussusception valves were made in the isolated loop of jejunum. There was no mortality. Only 1 case with infected wound and another case with the left underdiaphragmatic abscess caused by the leakage of the jejuno-jejunal anastomosis, successfully treated by the drainage of the abscess. All the patients normally discharged from the hospital

Clinical analysis of congenital bile duct dilatation / 中国普通外科杂志

Objective To summarize the etiology,classification and clinical characteristics of congenital bile duct dilatation and our experience in its diagnosis and troatment.Methods The clinical data of 37 cases of congenital bile duct dilatation were retrospectively analyzed.Results The 37 cases included TypeⅠin 31 cases,Type Ⅱ in 1 case,Type Ⅳ in 4 cases,and Type Ⅴ in 1case.All of the patients underwent operative treatment.External drainage of was done in 2 cases,Roux-en-y cystojejunostomy in 3 cases,exeisison of cyst cyst and Roux-en-y hepaticojejunostomy in 31 cases and left hepatectomy in 1case with malignant change of cyst.Five cases had postoperative complications that recovered with non-operative treatment.Thirty-two cases were cured.There were no operative deaths.Conclusions Congenital bile duct dilatation should be treated as soon as possible.Excision of the cyst and Roux-en-y hepaticojejunostomy can reduce long-term postoperative complications and is the rational treatment for congenital bile duct dilatation.